drugset / Trial / NCT02787044
INfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure
Phase 4
Completed
5388 enrolled
Brigham and Women's Hospital
Boston VA Research Institute, Inc. · collabNational Heart, Lung, and Blood Institute (NHLBI) · collabPatient-Centered Outcomes Research Institute · collabUniversity of Minnesota · collabUniversity of Toronto · collabUniversity of Wisconsin, Madison · collab
RandomizedParallel-groupQuadruple-blindPrevention
Summary
INVESTED will test the hypothesis that high dose trivalent influenza vaccine will reduce cardiopulmonary events to a greater extent than standard dose quadrivalent influenza vaccine in high-risk cardiovascular patients with a recent history of myocardial infarction or heart failure. The trial will enroll 9300 participants over one Vanguard (pilot) season and three additional influenza seasons. The primary endpoint will be a composite of all-cause mortality or cardiopulmonary hospitalization.
Timeline
- Start
- 2016-08-01
- Primary completion
- 2020-05-31
- Completion
- 2020-05-31
Publications
- Background Vardeny O, Sweitzer NK, Detry MA, Moran JM, Johnson MR, Hayney MS. Decreased immune responses to influenza vaccination in patients with heart failure. J Card Fail. 2009 May;15(4):368-73. doi: 10.1016/j.cardfail.2008.11.009. Epub 2008 Dec 18.
- Background Vardeny O, Moran JJ, Sweitzer NK, Johnson MR, Hayney MS. Decreased T-cell responses to influenza vaccination in patients with heart failure. Pharmacotherapy. 2010 Jan;30(1):10-6. doi: 10.1592/phco.30.1.10.
- Background Van Ermen A, Hermanson MP, Moran JM, Sweitzer NK, Johnson MR, Vardeny O. Double dose vs. standard dose influenza vaccination in patients with heart failure: a pilot study. Eur J Heart Fail. 2013 May;15(5):560-4. doi: 10.1093/eurjhf/hfs207. Epub 2013 Jan 4.
- Background Albrecht CM, Sweitzer NK, Johnson MR, Vardeny O. Lack of persistence of influenza vaccine antibody titers in patients with heart failure. J Card Fail. 2014 Feb;20(2):105-9. doi: 10.1016/j.cardfail.2013.12.008. Epub 2013 Dec 19.
- Background Udell JA, Farkouh ME, Solomon SD, Vardeny O. Does influenza vaccination influence cardiovascular complications? Expert Rev Cardiovasc Ther. 2015 Jun;13(6):593-6. doi: 10.1586/14779072.2015.1044439. Epub 2015 May 14.
- Background Vardeny O, Claggett B, Udell JA, Packer M, Zile M, Rouleau J, Swedberg K, Desai AS, Lefkowitz M, Shi V, McMurray JJV, Solomon SD; PARADIGM-HF Investigators. Influenza Vaccination in Patients With Chronic Heart Failure: The PARADIGM-HF Trial. JACC Heart Fail. 2016 Feb;4(2):152-158. doi: 10.1016/j.jchf.2015.10.012. Epub 2015 Dec 30.
- Background Udell JA, Zawi R, Bhatt DL, Keshtkar-Jahromi M, Gaughran F, Phrommintikul A, Ciszewski A, Vakili H, Hoffman EB, Farkouh ME, Cannon CP. Association between influenza vaccination and cardiovascular outcomes in high-risk patients: a meta-analysis. JAMA. 2013 Oct 23;310(16):1711-20. doi: 10.1001/jama.2013.279206.
- Background Vardeny O, Udell JA, Joseph J, Farkouh ME, Hernandez AF, McGeer AJ, Talbot HK, Bhatt DL, Cannon CP, Goodman SG, Anand I, DeMets DL, Temte J, Wittes J, Nichol K, Yancy CW, Gaziano JM, Cooper LS, Kim K, Solomon SD. High-dose influenza vaccine to reduce clinical outcomes in high-risk cardiovascular patients: Rationale and design of the INVESTED trial. Am Heart J. 2018 Aug;202:97-103. doi: 10.1016/j.ahj.2018.05.007. Epub 2018 May 23.
- Results Vardeny O, Kim K, Udell JA, Joseph J, Desai AS, Farkouh ME, Hegde SM, Hernandez AF, McGeer A, Talbot HK, Anand I, Bhatt DL, Cannon CP, DeMets D, Gaziano JM, Goodman SG, Nichol K, Tattersall MC, Temte JL, Wittes J, Yancy C, Claggett B, Chen Y, Mao L, Havighurst TC, Cooper LS, Solomon SD; INVESTED Committees and Investigators. Effect of High-Dose Trivalent vs Standard-Dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients With High-risk Cardiovascular Disease: A Randomized Clinical Trial. JAMA. 2021 Jan 5;325(1):39-49. doi: 10.1001/jama.2020.23649.
- Lassen MCH, Howell N, Claggett BL, Biering-Sorensen T, Vardeny O, Solomon SD, Udell J, Joseph J, Hegde SM. Educational Attainment Level and Risk of Mortality and Cardiopulmonary Outcomes in High-Risk Patients With Cardiovascular Disease: The INVESTED Trial. J Am Heart Assoc. 2025 Jul;14(13):e040221. doi: 10.1161/JAHA.124.040221. Epub 2025 Jun 18.
- Peikert A, Claggett BL, Udell JA, Joseph J, Hegde SM, Kim K, Mao L, Wang T, Havighurst TC, Farkouh ME, Bhatt DL, Tattersall MC, Cooper LS, Solomon SD, Vardeny O. Influenza Vaccine Immune Response in Patients With High-Risk Cardiovascular Disease: A Secondary Analysis of the INVESTED Randomized Clinical Trial. JAMA Cardiol. 2024 Jun 1;9(6):574-581. doi: 10.1001/jamacardio.2024.0468.
- Hegde SM, Claggett BL, Udell JA, Kim K, Joseph J, Farkouh ME, Peikert A, Bhatt AS, Tattersall MC, Bhatt DL, Cooper LS, Solomon SD, Vardeny O. Temporal Association Among Influenza-Like Illness, Cardiovascular Events, and Vaccine Dose in Patients With High-Risk Cardiovascular Disease: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 Sep 5;6(9):e2331284. doi: 10.1001/jamanetworkopen.2023.31284.
- Wang T, Mao L. Stratified proportional win-fractions regression analysis. Stat Med. 2022 Nov 20;41(26):5305-5318. doi: 10.1002/sim.9570. Epub 2022 Sep 14.
- Vardeny O, Hernandez AF, Cohen LW, Franklin A, Baqai M, Palmer S, Bierer BE, Cobb N. Transitioning to the National Institutes of Health single institutional review board model: Piloting the use of the Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance. Clin Trials. 2019 Jun;16(3):290-296. doi: 10.1177/1740774519832911. Epub 2019 Mar 13.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | High Dose Trivalent Influenza Vaccine | Vaccine | — | — |
| Comparator | Standard Dose Quadrivalent Influenza Vaccine | Vaccine | — | — |